Newsletter 4:2021

November 1, 2021

Dear Colleague

We reported on the improvement in transplant success rates on several occasions over the years (CTS Newsletter 2:2000, 3:2014, and 3:2019; Transplantation paper by G. Opelz in 2013 [doi:10.1097/‌TP.0b013e3182754c88]). In this newsletter, we want to look more closely at the changes of mortality risk of transplant patients over a period of 30 years. For this purpose, we analyzed 177,303 first deceased donor kidney transplants performed in Europe between 1988 and 2017. One of the simplest approaches is a Kaplan-Meier analysis of patient survival time for the categorized transplant years.

Figure 1 depicts a strong improvement with respect to patient survival in the period 1993–1997 compared to 1988–1992, while no large differences are evident thereafter. The greatest influence on mortality is the age of the patient, along with factors such as geographic origin of the patient and gender. Over the period of 30 years considered here, the average age of the patients at the time of transplantation steadily increased from 41.3 years in 1988 to 53.5 years in 2017. When adjusted for patient age, gender and country of origin using Cox regression, the survival curves shown in Figure 2 confirm impressively the continuous improvement in patient survival already referred to in CTS Newsletter 3:2014.

Only the CTS transplant cohort was included in the analyses shown in Figures 1 and 2, and it was not taken into account that in the non-transplant population the mean age also increased during the 30-year time period and age- and gender-specific mortality decreased. We now want to address the question of how the survival of transplant patients changed compared to the normal population. For this comparison, we used the Human Mortality Database (HMD, University of California, Berkeley, USA, and Max Planck Institute for Demographic Research, Germany, available at www.mortality.org, data downloaded April 22, 2021), which provides mortality rates for each country, gender, age and calendar year. To account for patient aging, we generated a data set for each calendar year (1,563,347 records) and assigned expected mortality from HMD to the transplanted patients with their actual age (Figure 3).

We would like to emphasize that the abscissa in Figure 3 is the actual age of the transplanted patients with a functioning graft and not the age at the time of transplantation. Relating the observed mortality of transplanted patients to the expected mortality, we obtain the standardized mortality ratio (SMR) as a measure of increased mortality risk (Figure 4).

An impressive reduction of the mortality risk SMR from 106.2 to 14.9 can be observed during childhood and adolescence, and the SMR continues to decrease to 2.1 in the highest age group ≥80.

Another confounder that needs to be considered in the analysis of mortality is the time after transplantation. It is known that the mortality in the first year post-transplant is higher than in subsequent years.

Similar curves to the one depicted in Figure 5, which shows a reduction of more than 50% in the second year for the age group 40–59, are found for the 18–39 age group (SMR reduction from 16.5 to 7.6), and the 60+ age group (SMR reduction from 5.7 to 2.5) (not shown). This points out the necessity to analyze mortality in short and long-term follow-up separately.

Figure 6 shows the overall more than 50% reduction in SMR (from 11.8 to 5.0) for the first post-transplant year over the 30 year-observation period 1988–2017. Interestingly, the improvements in the 1990s were somewhat greater than those in the current millennium.

A decrease of mortality risk was also found for post-transplant years 2 to 5 during the same observation period, although to a lesser extent of about 30% (Figure 7).

In summary, we are pleased that with this report we can share with you solid evidence for a continued progress of transplantation medicine regarding the reduction of mortality in renal transplant patients.

As a personal note, I would like to introduce myself as the Interim Coordinator of the CTS, after my colleague Caner Süsal left our institute at the end of August this year. As Caner announced in the last CTS Newsletter, he was appointed to the European Research Area Chair of Transplant Immunology at the Koç University in Istanbul. We thank Caner for his work dedicated to the CTS as CTS Coordinator over the last six years and wish him success in his new commitment. We are very fortunate that Gerhard Opelz remains our adviser, supporting us with his enormous long-standing expertise. In addition, our experienced CTS staff in Heidelberg (including our knowledgeable senior mathematician Bernd Döhler) pursue their work with unchanged enthusiasm and ensure the well-established quality of the database. I myself have been a member of the CTS staff and the Transplantation Immunology Working Group in Heidelberg since 2003, and I am therefore very familiar with the CTS themes and goals. It is a great honor for me to work with you and I am very much looking forward to a fruitful cooperation, aiming at serving our scientific community and, ultimately, our patients.

Please note that the Covid-19 and Biomarker Studies are still open for participation and you are very welcome to send us serum and DNA. Do not hesitate to contact us for any questions.

Thank you for your continued support and best wishes,

Hien Tran